rs387906744

Positions:

• chr5-58975718-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3 PP5

The NM_001104631.2(PDE4D):​c.1952A>C​(p.Glu651Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PDE4D NM_001104631.2 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 8.00

Genes affected

PDE4D (HGNC:8783): (phosphodiesterase 4D) This gene encodes one of four mammalian counterparts to the fruit fly 'dunce' gene. The encoded protein has 3',5'-cyclic-AMP phosphodiesterase activity and degrades cAMP, which acts as a signal transduction molecule in multiple cell types. This gene uses different promoters to generate multiple alternatively spliced transcript variants that encode functional proteins.[provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.797
• PP5: Variant 5-58975718-T-G is Pathogenic according to our data. Variant chr5-58975718-T-G is described in ClinVar as [Pathogenic]. Clinvar id is 30040.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE4D	NM_001104631.2	c.1952A>C	p.Glu651Ala	missense_variant	14/15	ENST00000340635.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE4D	ENST00000340635.11	c.1952A>C	p.Glu651Ala	missense_variant	14/15	1	NM_001104631.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Acrodysostosis 2 with or without hormone resistance Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jan 01, 2001

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.59
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Pathogenic	30
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.86	D;T;T;.;.;.;.;.;.;.;.
Eigen	Benign	0.11
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.97	D;D;D;D;D;D;D;D;D;D;D
M_CAP	Uncertain	0.20	D
MetaRNN	Pathogenic	0.80	D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Uncertain	-0.19	T
MutationAssessor	Benign	1.1	L;.;.;.;.;.;.;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D;D
PrimateAI	Pathogenic	0.84	D
PROVEAN	Pathogenic	-5.6	D;.;.;D;D;D;D;D;D;D;D
REVEL	Pathogenic	0.69
Sift	Uncertain	0.025	D;.;.;D;D;D;D;D;D;D;D
Sift4G	Benign	0.10	T;T;.;T;T;T;T;T;T;T;.
Polyphen		0.0050	B;.;.;.;P;.;B;B;P;P;.
Vest4		0.60
MutPred		0.48		Gain of MoRF binding (P = 0.0678);.;.;.;.;.;.;.;.;.;.;
MVP		0.88
MPC		1.9
ClinPred		0.99	D
GERP RS		3.2
Varity_R		0.84
gMVP		0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs387906744; hg19: chr5-58271545;